Nanoconstructs as a versatile tool for detection and diagnosis of Alzheimer biomarkers.

The current review focuses towards the advancements made in the past decade in the field of nanotechnology for the early Alzheimer's disease (AD) diagnosis. This review includes the application of nanomaterials and nanosensors for the early detection of the main AD biomarkers (amyloid beta, phosphorylated tau, apolipoprotein E4 allele or APOE4, microRNAs, cholesterol, hydrogen peroxide etc) in biological fluids, to detect the biomarkers at a very low concentration ranging in pico, femto and even atto molar concentrations. The field of drug development has always aimed and is constantly working on developing disease modifying drugs, but these drugs will only succeed when given in the early disease stages. Thus, developing efficient diagnostic tools is of vital importance. Various nanomaterials such as liposomes; dendrimers; polymeric nanoparticles; coordination polymers; inorganic nanoparticles such as silica, manganese oxide, zinc oxide, iron oxide, super paramagnetic iron oxides; quantum dots, silver nanoparticles, gold nanoparticles, and carbon based nanostructures (carbon nanotubes, graphene oxide, nanofibres, nanodiamonds, carbon dots); Up-conversion nanoparticles; 2D nanomaterials; and radioactive nanoprobes have been used in constructing and improving efficiency of nano-sensors for AD biosensing at an early stage of diagnosis.

Development and optimization of locust bean gum and sodium alginate interpenetrating polymeric network of capecitabine.

OBJECTIVE: The objective of the study was to develop interpenetrating polymeric network (IPN) of capecitabine (CAP) using natural polymers locust bean gum (LBG) and sodium alginate (NaAlg). SIGNIFICANCE: The IPN microbeads were optimized by Box-Behnken Design (BBD) to provide anticipated particle size with good drug entrapment efficiency. The comparative dissolution profile of IPN microbeads of CAP with the marketed preparation proved an excellent sustained drug delivery vehicle. METHODS: Ionotropic gelation method utilizing metal ion calcium (Ca2+) as a cross-linker was used to prepare IPN microbeads. The optimization study was done by response surface methodology based Box-Behnken Design. The effect of the factors on the responses of optimized batch was exhibited through response surface and contour plots. The optimized batch was analyzed for particle size, % drug entrapment, pharmacokinetic study, in vitro drug release study and further characterized by FTIR, XRD, and SEM. To study the water uptake capacity and hydrodynamic activity of the polymers, swelling studies and viscosity measurement were performed, respectively. RESULTS: The particle size and % drug entrapment of the optimized batch was 494.37 ± 1.4 µm and 81.39 ± 2.9%, respectively, closer to the value predicted by Minitab 17 software. The in vitro drug release study showed sustained release of 92% for 12 h and followed anomalous drug release pattern. The derived pharmacokinetic parameters of optimized batch showed improved results than pure CAP. CONCLUSION: Thus, the formed IPN microbeads of CAP proved to be an effective extended drug delivery vehicle for the water soluble antineoplastic drug.

Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers' Understanding to Improve Health Care.

INTRODUCTION: Japanese encephalitis (JE) is a major cause of high morbidity and mortality in several states across India. However, in 2014, a sharp rise was observed in the number of cases of JE in north-eastern Assam state, and 51% of the total cases of JE in India were reported from the Assam in the same year. In this regard, a study was conducted to evaluate the knowledge and attitudes of healthcare workers in Darrang, a district of Assam highly affected by JE. METHODS: A cross sectional study was conducted for 2 months among HCWs in the major district hospital of Darrang, Assam. A pre-tested, self-administered questionnaire was used to collect data from the participants. Convenience sampling approach was used to collect data from different departments of the hospitals. Descriptive and logistic regression analyses were used to express the results. RESULTS: The knowledge of HCWs regarding JE was poor with a mean knowledge score of 11.02±2.39 (out of 17), while their attitudes were positive with a mean attitudes score of 43.16± 2.47 (ranging from 13 to 52). Overall, 40.4% and 74.3% of participants demonstrated good knowledge and positive attitudes respectively. Cut-off score for good knowledge and positive attitudes toward JE was set as ≥12 and >40 respectively. Older participants (40-49 years) and experienced workers (>10 years) were significantly associated with good knowledge as compared to their referent group (p<0.05), while knowledge of nurses and other orderlies were significantly lower than physicians (p<0.01). Similar factors were associated with the positive attitudes of the participants with the exception of experience. Television was the major source of information regarding JE reported by HCWs (79%). CONCLUSION: Although the knowledge was not optimized, HCWs exhibited positive attitudes towards JE. Future research is required to design, implement and evaluate interventions to improve the knowledge of JE among HCWs.

Knowledge, attitude and practice of B.Sc. Pharmacy students about antibiotics in Trinidad and Tobago.

OBJECTIVE: The aim of this study was to assess the knowledge, attitude and practice of B.Sc. Pharmacy students about usage and resistance of antibiotics in Trinidad and Tobago. METHODS: This was a cross-sectional questionnaire-based study involving B.Sc. Pharmacy students. The questionnaire was divided into five components including Demographics data, knowledge about antibiotic use, attitude toward antibiotic use and resistance, self-antibiotic usage and possible causes of antibiotic resistance. Data were analyzed by employing Mann-Whitney and Chi-square tests using SPSS version 20. FINDINGS: The response rate was 83.07%. The results showed good knowledge of antibiotic use among students. The overall attitude of pharmacy students was poor. About 75% of participants rarely use antibiotics, whereas self-decision was the major reason of antibiotic use (40.7%) and main source of information was retail pharmacist (42.6%). Common cold and flu is a major problem for which antibiotics were mainly utilized by pharmacy students (35.2%). CONCLUSION: The study showed good knowledge of pharmacy students regarding antibiotic usage. However, students' attitude towards antibiotic use was poor. The study recommends future studies to be conducted with interventional design to improve knowledge and attitude of pharmacy students about antibiotic use and resistance.

Significance of pharmaceutical excipients in prescribed medicines: a case report.

KEY CLINICAL MESSAGE: Pharmaceutical excipients need careful observation as they play a significant role in treatment outcomes. It is imperative for a physician to collect complete patient profile before prescribing new medications for current treatment. We present a case report on the significance of pharmaceutical excipients in prescribed medicines.

Impact of chronic disease assistance program on the retail pharmacy sector: A retrospective study.

OBJECTIVE: To assess the impacts of chronic disease assistance program (CDAP) on economic parameters, human resource and pharmacy structure and pharmaceutical care on the retail industry in Trinidad and Tobago. MATERIALS AND METHODS: A partially perceptual retrospective investigation was carried out in 60 pharmacies from all regions (North East, North West, Central and South) in Trinidad. Questionnaires were distributed to all pharmacists of the each pharmacies indicated above. The validated questionnaires were distributed, over a period of approximately 2 weeks. Pharmacists employed at each pharmacy were asked to complete the questionnaire which consisted of 11 questions based on the three aspects of investigation. A five-point Likert scale (1 = strongly disagree, 5 = strongly agree) was used. Information from the completed questionnaires was tabulated in Microsoft Excel and the respective percentages and proportions were generated. RESULTS: From the 60 pharmacies, 61% (n=37) believed that there was a decrease in sale of original brands while more than half of the respondents [53% (n=32)] believed there was an increase in sale of generics. The 60% (n=36) respondents viewed that there was compromised dispensary sale of original brands while 65% (n=39) felt there was increased orders for generic drugs. Of the CDAP prescriptions, it was disclosed that there was an overall increase in CDAP prescriptions from the year 2005-2008. A medium-scale pharmacy disclosed 1801 prescriptions in 2005, 2265 prescriptions in 2006, 3002 prescriptions 2007 and 3344 prescriptions in 2008 with overall increase in each year. CONCLUSIONS: The implementation of CDAP can explain the phenomenal increase in sale of generics drugs and the decrease in the sale of brands. There is a need for such a program in the developing countries.

Novel liquid chromatographic method for simultaneous estimation of pioglitazone and glimepiride in rat plasma by solid phase extraction: application to preclinical pharmacokinetic studies.

The need for a reliable bioanalytical method is of primary importance during preclinical studies. The aim of the present study was simultaneous determination of pioglitazone (CAS 111025-46-8) (PIO) and glimepiride (CAS 93479-97-1) (GLM) in plasma of rats. A high-performance liquid chromatographic method has been developed and validated using C18 column and UV detector. A mobile phase composed of acetonitrile and ammonium acetate buffer pH 4.5 in the ratio of 55:45%. The plasma samples clean-up was carried out using solid phase cartridges. The method was in the linear range of 50-8000 ng/mL for PIO and 50-2000 ng/mL for GLM. The coefficient of regression was found to be > or = 0.99. Precision and accuracy were within the acceptable limits, as indicated by relative standard deviation varying from 1.5 to 6.1% for PIO and 3.1 to 7.0% for GLM whereas the accuracy ranged from 97.0 to 106.4% for PIO and 96.5 to 106.4% for GLM. The mean extraction recovery was found to be 90.2 +/- 4.5, 76.8 +/- 2.8 and 85.2 +/- 5.2% for PIO, GLM and internal standard, respectively. Moreover, PIO and GLM were stable in plasma, up to 30 days of storage at -70 degrees C and after being subjected to bench top, auto-sampler, and three freeze-thaw cycles. The developed method was applied for preclinical pharmacokinetic studies.

Sodium glucose Co transporter 2 (SGLT2) inhibitors: a new sword for the treatment of Type 2 Diabetes Mellitus

The low affinity sodium glucose cotransporter (SGLT2) plays a major role in physiology of glucose re-absorption from proximal part of kidney. Almost all glucose excreted through glomerular filtration, is re-absorbed via SGLT2 until blood glucose level reaches to its threshold value for glucose excretion i.e. - 180mg/dl. Increasing the glucose excretion by inhibiting the SGLT2 is the novel approach for the treatment of diabetes. Safe and normal life of patients having familial renal glucosuria due to SLC5A2 gene mutation is accelerating the development of SGLT2 inhibitors. Weight loss and very low risk of hypoglycemia are the potential benefits of these inhibitors. There are number of molecules in this class under the stage of development.

Enhanced dissolution and bioavailability of gliclazide using solid dispersion techniques

Gliclazide is practically insoluble in water and its bioavailability is limited by dissolution rate. To enhance the dissolution rate and bioavailability the present study was aimed to formulate solid dispersions using different water soluble polymers such as polyethylene glycol 4000 (PEG 4000), polyethylene glycol 6000 (PEG 6000) using fusion method and polyvinyl pyrrolidone K- 30 (PVP K 30) by solvent evaporation method. The interaction of gliclazide with the hydrophilic polymers was studied by Differential Scanning Calorimetry (DSC), Fourier Transformation-Infrared Spectroscopy (FTIR) and X-Ray diffraction analysis. Solid dispersions were characterized for physicochemical properties like drug content, surface morphology and dissolution studies. Various factors like type of polymer and ratio of the drug to polymer on the solubility and dissolution rate of the drug were also evaluated. Pharmacokinetic studies of optimized formulation were compared with pure drug and marketed formulation in wistar rats. The dissolution of the pure drug and solid dispersion prepared with PVP K 30 (1:1) showed 38.3 + 4.5 % and 95 + 5.2 % release respectively within 30 min. Peak plasma concentration of pure drug, solid dispersion (PVP K 30) and marketed formulation was found to be 8.76 + 2.5, 16.04 + 5.5 and 9.24 + 3.6 g/ml respectively, from these results it was observed that there is two fold increase in peak plasma concentration compared to pure drug. Solid dispersion is an effective technique in increasing solubility, dissolution rate and bioavailability of the poorly soluble drugs.

Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: a preliminary study.

The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 +/- 4 kg m(-1) S(-2) and more than 2.5 kg/3 cm(2), respectively. The percent drug content was 98.5 +/- 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically.

Effect of concomitant atropine and glycopyrrolate infusion in organophosphorus poisoning

AIM : To study the effectiveness of concomitant atropine and glycopyrrolate infusion over atropine infusion in organophosphorus (OP) poisoning. METHODS : A prospective randomized study was carried out among 60 OP poisoned patients admitted to an emergency department of tertiary care hospital in south India. All patients admitted with acute OP poisoning were enrolled in the study. They were randomized into test group and control group of 30 patients each. Patients who received only atropine alone were randomized as control group and patients who received concomitant glycopyrrolate were enrolled in the test group. All patients were provided 1g pralidoxime every eighth hourly treatment. The severity was assessed using GCS, APACHE II, and PSS scores at admission. The outcomes were accessed in terms of intermediate syndrome, ventilation period, total dose and duration of atropine, atropine toxicity, incidence of pneumonia,hospitalization period and mortality.

Review: dalbavancin--a novel lipoglycopeptide antimicrobial for gram positive pathogens.

Glycopeptide antibiotics represent an important class of microbial compounds produced by several genera of actinomycetes. The emergence of resistance to glycopeptides among enterococci and staphylococci has prompted the search for second-generation drugs of this class and semi-synthetic derivatives are currently under clinical trials. Antimicrobial resistance among gram-positive organisms has been increasing steadily during the past several decades. Dalbavancin, a novel lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has in vitro activity against a variety of Gram-positive organisms specially multidrug resistant Staphylococcus aureus, but no activity against Gram-negative or vancomycin-resistant enterococci that possess vanA gene. Due to its prolonged half-life (6-10 days), dalbavancin can be administered intravenously once weekly. In Phase II and III clinical trials, dalbavancin was effective and well-tolerated for the treatment of skin and soft-tissue infections, catheter-related bloodstream infections, and skin and skin-structure infections. To date, adverse events have been mild and limited; the most common being pyrexia, headache, diarrhea. Dalbavancin appears to be a promising antimicrobial agent for the treatment of Gram-positive infections. Additional clinical data are required to fully assess its use. Despite the remarkable and favorable pharmacokinetic and pharmacodynamic properties, the use of this potent agent should be restricted to severe infections due to multidrug resistant organisms to limit the risk of selection of resistance. It is active against Gram-positive aerobes and anerobes, including resistant pathogens, with the exception of strains producing vanA-mediated resistance. Its approval by the FDA is expected soon. The extent to which dalbavancin will supplant vancomycin and whether it will be preferred over other newer agents such as linezolid in the next decade remains to be seen.